Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets.

Pancreas transplantation is an option to achieve better metabolic control and decrease chronic complications in patients with diabetes. Xenotransplantation becomes an important alternative. In this study, we show the clinical outcome of patients with type 1 diabetes transplanted with neonatal pig islets without immunosuppression. In a longitudinal study of 23 patients with type 1 diabetes, who received porcine islets between 2000 and 2004, we registered demographic and clinical characteristics every 3 months and chronic complications evaluation yearly. Porcine C-peptide was measured in urine samples under basal conditions and after stimulation with l-arginine. More than 50% were female, median current age was 20·8 years, median diabetes duration at transplantation 5·5 years, median current diabetes duration 11 years and median time post-transplantation 5·7 years. Their media of glycosylated haemoglobin reduced significantly after the first transplantation. Insulin doses remain with a reduction greater than 33% in more than 50% of the patients. Before transplantation, 14 of the 21 patients presented mild chronic complications and currently only two patients presented these complications. Porcine C-peptide was present in all urine samples under basal conditions and increased post-stimulation with l-arginine. These patients achieved an excellent metabolic control after the first transplantation. This could explain, as well as the remaining function of transplanted cells, the low frequency of chronic complications compared to patients with similar diabetes duration and age.

No evidence of porcine endogenous retrovirus in patients with type 1 diabetes after long-term porcine islet xenotransplantation.

Xenotransplantation is a promising alternative for donor shortage to ameliorate physiologic and metabolic disorders. The major concern for xenotransplant is the risk of zoonosis mainly by the porcine endogenous retrovirus (PERV), presentation in the piglet genome. Twenty-three patients with type 1 diabetes were transplanted with porcine islets using collagen-generating devices which were implanted subcutaneously in the anterior wall of the abdomen. Clinical characteristics and metabolic tests were recorded in each visit. They were tested for PERV using PCR and RT-PCR from blood pretransplantation and every 3 months during a 4.6- to 8-year follow-up after their first xenotransplant. Tests by PCR of every DNA sample (780 samples) revealed that there was no PERV infection in the DNA of white cells. No evidence of PERV activation was found in this group of patients with type 1 diabetes during clinical long-term follow-up.

Three-yr follow-up of a type 1 diabetes mellitus patient with an islet xenotransplant.

In order to alleviate the shortage of human donors, the use of porcine islets of Langerhans for xenotransplantation in diabetic patients has been proposed as a solution. To overcome rejection, we have developed a procedure for protecting the islets by combining them with Sertoli cells and placing them in a novel subcutaneous device, that generates an autologous collagen covering. A type 1 diabetic woman was closely monitored for 10 months, and then transplanted in two devices with two months of difference and a third time after 22 months. Here we present a three-yr follow-up. The close monitoring induced a rapid decrease in exogenous insulin requirements, which stabilized between 19 and 28 IU/d for nine months. After transplantation, the requirements reduced further to below 6 IU/d and for some weeks she was insulin free. Glycosylated hemoglobin levels decreased concomitantly. Porcine insulin could be detected in the serum after a glucose challenge and insulin positive cells inside a removed device after two yr. No complications have arisen and no porcine endogenous retrovirus infection has been detected through PCR and RT-PCR. This case demonstrates the feasibility of using the xenotransplantation of porcine cells to alleviate metabolic complications and insulin requirements in type 1 diabetic patients.

Psychosocial aspects of xenotransplantation: survey in adolescent recipients of porcine islet cells.

INTRODUCTION: Transplantation is a process with several psychosocial challenges. Regarding the case of xenotransplantation, the perceived similarity between humans and pigs may be stressful. Adjustment disorders have been reported among transplantation recipients. We sought to assess the psychosocial aspects of xenotransplantation among porcine islet-cell recipients and their efforts to adapt themselves to this condition. MATERIAL AND METHODS: Ten insulin-dependent diabetes mellitus patients aged 14.58 +/- 7.93 who received porcine islet-cells were included. The bioartificial steel/fibrous tissue chamber method was used. All patients and their relatives were interviewed about their expectations, overall functioning, and experiences. The quality of life, enjoyment, and satisfaction scale and the hospital anxiety and depression scales were used. A 1-year follow-up was done. RESULTS: Their motivation was centered on autonomy; there were no troubles regarding the graft origin. Xenotransplantation was perceived with pragmatism, seeing pigs as an unlimited resource. The patients with best outcomes also had the greatest improvements in several quality of life areas (QOL) while the medium responders had fewer QOL improvements. The nonresponders experienced mainly frustration. Parents' concerns were not related to their children's health but to their recently gained autonomy. CONCLUSIONS: In addition to enthusiasm, the perception of animals as an unlimited source of organs may affect patient compliance; in this group, xenotransplantation was seen as using as a long-lasting drug, with chamber walls considered as a physical, immunologic, and, in certain manner, a psychological barrier.